The UPF1 RNA Surveillance Gene Is Commonly Mutated in Pancreatic Adenosquamous Carcinoma

Nat Med. 2014 Jun;20(6):596-8. doi: 10.1038/nm.3548. Epub 2014 May 25.

Abstract

Pancreatic adenosquamous carcinoma (ASC) is an enigmatic and aggressive tumor that has a worse prognosis and higher metastatic potential than its adenocarcinoma counterpart. Here we report that ASC tumors frequently harbor somatically acquired mutations in the UPF1 gene, which encodes the core component of the nonsense-mediated RNA decay (NMD) pathway. These tumor-specific mutations alter UPF1 RNA splicing and perturb NMD, leading to upregulated levels of NMD substrate mRNAs. UPF1 mutations are, to our knowledge, the first known unique molecular signatures of pancreatic ASC.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / genetics*
  • Base Sequence
  • Carcinoma, Adenosquamous / genetics*
  • Gene Components
  • HEK293 Cells
  • Humans
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Molecular Sequence Data
  • Mutagenesis
  • Mutation / genetics
  • Nonsense Mediated mRNA Decay / genetics*
  • Pancreatic Neoplasms / genetics*
  • RNA Helicases
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Analysis, DNA
  • Trans-Activators / genetics*

Substances

  • Trans-Activators
  • RNA Helicases
  • UPF1 protein, human

Supplementary concepts

  • Pancreatic Carcinoma

Associated data

  • GENBANK/KJ850256
  • GENBANK/KJ850257
  • GENBANK/KJ850258
  • GENBANK/KJ850259
  • GENBANK/KJ850260
  • GENBANK/KJ850261
  • GENBANK/KJ850262
  • GENBANK/KJ850263
  • GENBANK/KJ850264
  • GENBANK/KJ850265
  • GENBANK/KJ850266
  • GENBANK/KJ850267
  • GENBANK/KJ850268
  • GENBANK/KJ850269
  • GENBANK/KJ850270
  • GENBANK/KJ850271
  • GENBANK/KJ850272
  • GENBANK/KJ850273